Recent studies suggest that the same compound may have both endocrine and neurocrine functions, and thus, presumed neurotransmitters may also function as hormones. Serotonin and substance P, both products of the intestinal enterochromaffin cells, have been shown to have potent and similar humoral effects on the gastrointestinal tract. However, to date, these effects have been incompletely evaluated and it is not clear whether these are physiological. This proposal utilizing radioimmunoassays for these hormones is designed to 1. evaluate the stimuli for release of intestinal serotonin and substance P into the systemic circulations, 2. Assess the effects of these humoral agents in dogs on a) gastric secretion of acid and pepsin, b) intestinal motility, electrical activity, and absorption of electrolytes, c) pancreatic secretion of electrolytes and enzymes, and d) release of insulin and glucagon by infusion to reproduce levels achieved during physiologic release; 3. determine their biologically active molecular forms and 4. establish their biological half-lives and site(s) of inactivation. In addition to their intestinal actions, serotonin and substance P have vasomotor effects, and thus, they may be implicated in the dumping and carcinoid syndromes. By studying patients who have undergone gastrectomy and/or vagotomy including those with dumping syndrome and asymptomatic controls, postoperative serotonin and substance P responses to standard meals, calcium infusion and irrigation of the proximal small intestine with hypertonic glucose will be characterized to evaluate the role of these agents in the dumping syndome. Finally, peripheral blood concentrations of serotonin and substance P in patients with carcinoid tumors will be correlated with their symptoms in order to assess the role of these agents in the carcinoid syndome.